Flow-induced conformational change of von Willebrand Factor multimer: Results from a molecular mechanics informed model

A special instrument for the defined modification of polymer properties in solutions and polymer layers

“…It is well known that polymer systems can exhibit viscoelastic behaviour with possible memory response (i.e., thixotropy) when exposed to shear stress [50][51][52]. With respect to these facts, the self-organised flow in BM-cells or RB-cylinders might be utilized for the targeted straining of polymer systems, connected with an irreversible change in the polymer chain conformation [1,2,6,53]. The results in Figs.…”

“…Flow-induced conformation changes in flexible macromolecular systems have been repeatedly studied (and simulated) [1][2][3]. The action of such forces can result in irreversible changes in the tertiary and quaternary structures of macromolecular systems [4,5], thereby determining the physicochemical properties of individual chains and the system as a whole [5][6][7][8].…”

Internal Tensile Force and A2 Domain Unfolding of von Willebrand Factor Multimers in Shear Flow

“…Data were collected for 30 , after the first was discarded to ensure no transient effects were considered in the averaged data. The initialization process is described in more detail in [14]. A multimer's elongation relaxation time, , is based on the time required for an elongated chain to return to a globule [29]- [31], which increases with length and was determined previously in [14].…”

“…By examining data for the duration and location of significant force excursions, convincing evidence is advanced that unfolding of A2 domains, and therefore scission of vWF multimers by the size-regulating blood enzyme ADAMTS13, happen preferentially near the center of unraveled multimers. the folded A2 domain structure [14], [16]- [19]. The A2 domain remains folded under a threshold tensile force, making it unsusceptible to scission.…”

“…For this reason, we have previously introduced a coarse-grained model that attempts to more realistically describe the molecular architecture inherent to vWF in order to better capture its internal dynamics, namely A2 domain dynamics [14]. While coarse-grained, our model achieves increased fidelity by explicitly modeling the A2 domain, which has been shown to unfold significantly under sufficient force [4].…”